Ketomalonic acid diesters or hydrates thereof are useful compounds as raw materials in the production of pyrazine-2-one-3-carboxylic acid ester derivatives through the reaction with diamines (see Patent Documents 1 to 4 and Non Patent Documents 1 and 2). This reaction is utilized in the production of pharmaceuticals, agricultural chemicals, and the like particularly as a method of producing quinoxalinone derivatives from aromatic diamines.
Conventionally, direct or indirect methods have been reported as the method of synthesizing ketomalonic acid diesters from malonic acid diesters. However, both of them have a problem. As the method of synthesizing ketomalonic acid diesters from malonic acid diesters, for example, a method is known in which a ketomalonic acid diester is produced by oxidizing a malonic acid diester with an oxidizing agent such as selenium dioxide (for example, see Non Patent Document 3), dinitrogen trioxide (for example, see Non Patent Document 4), or chromium trioxide (for example, see Non Patent Document 6). However, all of those methods have problems such as severe toxicity of reagents, a difficulty in handling of reagents, and the like.
In addition, methods of producing a ketomalonic acid diester such as a method in which a compound obtained by substituting the active methylene moiety of a malonic acid diester with bromine is reacted with silver nitrate (for example, see Non Patent Document 7), a method in which a compound obtained by substituting the active methylene moiety of a malonic acid diester with an azo group is reacted with dimethyldioxirane (for example, see Non Patent Document 8), a method in which a compound obtained by substituting the active methylene moiety of a malonic acid diester with a methylene group is reacted with ozone (for example, see Non Patent Documents 5 and 9), and a method in which a compound obtained by substituting the active methylene moiety of a malonic acid diester with a hydroxyl group is reacted in the presence of a precious metal catalyst (for example, see Patent Document 5) are also known. However, in these methods, there is a drawback that tartronic acid that is much more expensive than malonic acid diesters is used as a raw material or the active methylene moiety of a malonic acid diester is required to be modified in advance. Hence, there are economic and operational problems in these methods. In addition, there is a problem of using an expensive reagent, a special reagent, an expensive catalyst, or a transition metal in these methods.
Furthermore, a method has been reported in which a malonic acid diester is reacted with sodium chlorite (see Patent Document 6). The method described in Patent Document 6 is superior to conventional methods known before Patent Document 6, but there is still room for improvement in consideration of economic and environmental aspects as to be described later.